Departments of Pediatrics and Neonatology, University of Rochester Medical Center, Rochester, New York, USA.
Int J Radiat Biol. 2011 Aug;87(8):902-13. doi: 10.3109/09553002.2011.573439. Epub 2011 May 17.
In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge.
C57BL/6J mice received total body irradiation (0.5-10 Gy) and were followed for 6-18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]).
Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls.
We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.
在我们对放射性恐怖主义或核扩散事件后果的持续调查中，我们评估了一个被认为是肺终点发展的亚阈值剂量范围是否会导致晚期病理变化，其次，这些晚期变化是否会影响肺部对后续挑战的反应能力。
C57BL/6J 小鼠接受全身照射（0.5-10Gy），并在照射后 6-18 个月进行随访。在 12 个月和 15 个月时，一部分小鼠接受了第二次挑战（气溶胶脂多糖[LPS]）。
照射后数小时（IL-6、角质细胞趋化因子[KC]、IL1B 和 IL1R2）被证明上调的细胞因子在晚期（9 个月）时表现出信使核糖核酸（mRNA）表达的持续、剂量依赖性增加。尽管观察到 T 细胞计数持续增加，但未观察到其他明显的病理生理学变化。尽管如此，在晚期暴露于二次挑战的动物表现出与对照组相比炎症细胞募集和持续存在增加。
我们提出，在引起病理生理学变化很小的剂量下，亚临床辐射诱导的损伤增加了肺部对二次挑战的易感性，可能是通过辐射诱导的免疫系统防御改变。
